I’m at the Harvard probiotics symposium the next couple of days. 
Microbiota produce short chain fatty acids from fiber we eat. Researchers discovered that fiber-fed mouse models of food allergy and type I DM had lower levels of disease.
...so they skipped the middle man and just fed the mice precursors of short chain fatty acids and they were even more protective.
They did the same thing for mouse models of asthma, but to pregnant mice, and their pups had much lower levels of asthma. (Trying to picture an asthmatic mouse 😕). The fiber affected gene expression in the fetal lung tissue.
Mackay postulates mechanism: T cells get a tuning as they go through the portal vein hepatic circulation and higher levels of butyrate and acetate are protective against autoimmunity (doesn’t have this proven yet)
Next talk is about maternal-fetal interactions and microbiome. Dr. Erika Isolauri is from Finland.
First off: fetuses are not in a sterile environment. Placenta is colonized with microbes, these same microbes are seen in baby’s meconium as well.
In pregnancy diversity of the microbiota decreases and population changes. transferring the microbiome of a third trimester pregnant to a mouse causes the mouse to gain weight! The transfer of microbiome of first trimester women does not.
Now some data on C Section delivery increasing risks of disease...things like asthma and obesity. Lots of confounders but c section also increases exposure to antibiotics in delivery.
Another interesting tidbit...microbiome is more different in babies born by elective c section than emergency c section to babies born with vaginal delivery suggesting contractions or hormones of labor may play a role.
Cool...this prof’s group did this really interesting 13 year study: psychologytoday.com/us/blog/evolut…
C section rates around the world: Finland 15%, USA 30%, China and Mexico 60%, Brazil 80%
Dr. Isolauri says she did 5 years of preclinical studies before her small studies of probiotics in moms/infants to carefully select strains that seemed to have anti inflammatory and immune modularity properties.
A question from a nutritionist here at HSPH...is the very high rate of obesity later in life of premature infants due in part to microbiome differences? (No answer yet but interesting question)
Next up is Eline M van der Beek, PhD from the Netherlands, university medical center Groningen on early life nutrition and gut microbiome.
Infant growth in the first 1000 days is crazypants
Humans (should) reach peak adiposity at 6-9 months of age (healthy infants this age are 27% fat).
Breastfed infants gain *more* weight 0-4 months and have less weight gain in late infancy than formula fed infants. They are trying to figure out the components of breast milk that affect baby growth and later metabolic flexibility.
(I’m a firm believer in “fed is best” btw :)
Breast milk is 50-60% fat. Omega 6 increases the number of adipose cells whereas omega 3 reduces this effect, so change in fatty acid composition of breast milk over the years could have obesogenic effect.
In healthy mice given omega3s or restricted omega 6 as pups had similar body weight to control mice but less adiposity.
Milk processing and sterilization changes the lipids in milks, the lipid droplets are smaller, phospholipids are stripped off the coating. Prof created processed milk w/lipids with a phospholipid coating and fed to mouse pups, also had lower adiposity than pups fed processed milk
How does the microbiome affect metabolism? Multiple ways, but it can do so directly by affecting the bile acids that are made, changing the absorption and digestion of fats.
Another interesting study: took microbiota from Asian women of *normal weight* with GDM to mice and made them pregnant. These mice had *lower* glucose in pregnancy and greater insulin levels...
...suggesting perhaps the microbiome changes in women with gestational GM help protect mom and baby from hyperglycemia...
Next talk is on gut microbiota and malnutrition/undernourished kids from Sathish Subramanian MD PhD, currently a resident at MGH, so smart and also very tired.
Undernourishment is not just due to food insecurity, but also due to other inter generational factors including gut microbiome. Undernourished kids have reduced food absorption, impaired intestinal villae function, and are immune impaired.
Researchers sequenced gut bacteria of healthy kids and they could predict the age of the child 0-2 based on microbiome. (Infants and toddlers have rapidly changing microbiomes)...they cross validated the model in another group of healthy kids. (these studies done in Bangladesh)
Diarrhea disease will slow down the development of the microbiome for several months (from studies in human twins and triplets)
By age 5 the microbiome has mostly finished maturing. Early interventions may have more lasting effects than those in adults.
(Not mentioned in this talk but same is likely also true of parasitic exposure and it’s effects in autoimmunity, etc)
They were able to stunt the growth of germ free mice by giving them the microbiome of kids with kwashiokar...
